Phenol → (S)-tert-Butyl 2-(phenoxymethyl)pyrrolidine-1-carboxylate

HRID 1057520Notes

Reaction equation

HRID 1057520 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[H][H].[C:12]([N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[CH2:24]OS(C1C=CC(C)=CC=1)(=O)=O)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]>C1COCC1.CCOC(C)=O.CN(C=O)C>[C:12]([N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[CH2:24][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

8

Reactant 4

HCID 996PhenolHCID 24758Sodium hydrideHCID 11783214tert-Butyl (2S)-2-(((4-methylbenzene-1-sulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 10636271(S)-tert-Butyl 2-(phenoxymethyl)pyrrolidine-1-carboxylateYield 71%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of phenol (0.40 g, 4.23 mmol) in 10 mL of THF at 0° C. was added sodium hydride (0.226 g, 5.65 mmol), and the mixture was warmed to room temperature. The mixture was stirred 10 minutes (until evolution of hydrogen gas ceased) and cooled to 0° C. A solution of (S)-(+)-N-Boc-2-(4-toluenesulfonyloxymethyl)pyrrolidine (1.0 g, 2.8 mmol) in 2 mL of THF was added dropwise and the resulting mixture was refluxed overnight. To the mixture was added 5 mL of DMF and the mixture was heated at 100° C. overnight. To the mixture was added EtOAc and the organic layer was washed thrice with water, thrice with 1N NaOH, and twice with water. The organic layer was then dried over MgSO4, filtered and concentrated under reduced pressure to give an oil. The oil was purified by silica gel chromatography with 7% EtOAc/Hexanes to give the title compound as a colorless oil (0.55 g, 71%). ES (+) MS m/e=278 (M+H).

Workup

  1. temperaturecooled to 0° C
  2. temperaturethe resulting mixture was refluxed overnight
  3. temperaturethe mixture was heated at 100° C. overnight
  4. washthe organic layer was washed thrice with water, thrice with 1N NaOH
  5. dry with materialThe organic layer was then dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give an oil
  9. customThe oil was purified by silica gel chromatography with 7% EtOAc/Hexanes

Sources & evidence

ORD record
ord-8d1126ce46724cae8a88ee32096ffb9b
Source dataset
uspto-grants-2003_02
Patent number
US06514992B1

Reaction notes

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